Members of the section and collaborators completed initial SAR studies of two substituted compounds designed and synthesized for imaging signal transduction mechanisms with PET. We have determined that the recently synthesized fluorocarbonate derivative of forskolin retains activity and binds to adenylate cyclase with an affinity in the nanomolar range. Initial F-18 modeling studies have shown that we can expect an acceptable radiochemical yield. The compound is being tritiated for further in vivo studies. On the other hand, the recently synthesized fluoroisobutryate derivative of deoxyphorbol binds only in the micromolar range. We will attempt C-11 labeling of the native (unsubstituted) deoxyphorbol or attempt to label another PKC antagonist.